The major objectives of this proposal are to elucidate the metabolic roles of copper and zinc in animals. Nutritional deficiencies will be imposed and the resulting pathology studied. By this procedure one can then focus on biochemical pathways in which the respective element plays a critical and specific role. Copper has been shown to function as a catalyst in the crosslinking of collagen and elastin and thus in maintaining the integrity of major blood vessels. The biochemical defect is lack of lysyl oxidase activity. This enzyme has been isolated and shown to be a copper metalloenzyme. The immediate objective is to characterize lysyl oxidase more completely including its kinetic properties and substrate specificities. Copper deficiency also affects central nervous system function and the metabolic defect is related to catecholamine metabolism. The basis for decreased brain levels of catecholamines will be studied. Zinc deficiency has many physiological ramifications and there is no unifying hypothesis to explain zinc's critical metabolic role. In this proposal, attention will be focused on the role of zinc in the reproductive process.